Eating disorders in people with Type 1 diabetes: experiential perspectives of both clients and healthcare professionals.

AIMS: To explore the experiential perspective of people with Type 1 diabetes mellitus and eating disorders and that of the healthcare professionals treating them, and to understand the experience of both sides to inform future development of healthcare services. METHODS: Participants were recruited from Diabetics with Eating Disorders (a national UK charity), and through professional networks. Nine partially/fully recovered individuals with Type 1 diabetes and eating disorders and eight healthcare professionals participated in semi-structured interviews carried out by medically trained researchers. Data were transcribed and coded using a six-stage framework of thematic analysis. RESULTS: Four superordinate themes and several subordinate themes emerged from the Type 1 diabetes and eating disorders dataset: (1) perceptions surrounding service provision; (2) reflections on the recovery process; (3) the experiential perspective of living with Type 1 diabetes and an eating disorder; and (4) support mechanisms. Healthcare professional data elicited three superordinate themes and several subordinate themes: (1) service provision; (2) personal insight and reflection of professional role; and (3) challenges of working with dual diagnoses. CONCLUSION: People with Type 1 diabetes and eating disorders and their healthcare professionals provided insight into healthcare services from the patient and care delivery perspectives. There was general agreement from both groups that a multidisciplinary, collaborative (family inclusive), clinical approach to treatment is important, as well as adequate training opportunities for service providers. These findings may help to inform development strategies for multidisciplinary care approaches to Type 1 diabetes complicated by eating disorders.

GC-MS analysis of cuticular lipids in recent and older scavenger insect puparia. An approach to estimate the postmortem interval (PMI).

An analytical method was developed to characterize puparia cuticular lipids (hydrocarbons, waxes) and to compare the molecular distribution patterns in the extracts from either recent or older puparia. Acid-catalyzed transesterification and solvent extraction and purification, followed by combined gas chromatography coupled to mass spectrometry, were optimized for the determination of hydrocarbons and fatty acid ethyl esters from transesterified waxes, extracted from a single species of a fly scavenger (Hydrotaea aenescens Wiedemann, 1830). Comparison between recent (2012) or older (1997) puparia contents has highlighted significant composition differences, in particular, a general decrease of the chain length in the n-alkane distribution pattern and, on the contrary, an increase of the ester chain length. Both extracts contain traces of three hopane hydrocarbon congeners. Preliminary results evidence the change in puparia lipid composition over time, thus potentially providing new indices for estimating postmortem interval.

The mouse dystonia musculorum gene is a neural isoform of bullous pemphigoid antigen 1.

Dystonia musculorum (dt) is a hereditary neurodegenerative disease in mice that leads to a sensory ataxia. We describe cloning of a candidate dt gene, dystonin, that is predominantly expressed in the dorsal root ganglia and other sites of neurodegeneration in dt mice. Dystonin encodes an N-terminal actin binding domain and a C-terminal portion comprised of the hemidesmosomal protein, bullous pemphigoid antigen 1 (bpag1). dt and bpag1 are part of the same transcription unit which is partially deleted in a transgenic strain of mice, Tg4, that harbours an insertional mutation at the dt locus, and in mice that carry a spontaneous dt mutation, dtAlb. We also demonstrate abnormal dystonin transcripts in a second dt mutant, dt24J. We conclude that mutations in the dystonin gene are the primary genetic lesion in dt mice.

Heavy chain subclasses of human gamma G-globulin. Serum distribution and cellular localization.

Two antigenic types of naturally occurring proteins related to the papain produced F(c) fragment of gammaG-globulin have been studied. Most normal and myeloma gammaG-globulins are related to one or the other of these proteins, based on antigenic and structural characteristics of their heavy chain. Molecules bearing the determinant "Cr" are approximately 10 times as abundant as those bearing the determinant termed "Zu" in pools of normal gammaG-globulin and among a large group of gammaG-myeloma globulins. Both populations have properties of typical gammaG-globulin antibodies. Splenic cells, stained for these two populations with specific fluorescent antibody preparations, are found to contain one or the other of the two populations of gammaG-globulin, but not both. Approximately 10 times as many cells contain the Cr determinant as contain the Zu determinant.

Six6 (Optx2) is a novel murine Six3-related homeobox gene that demarcates the presumptive pituitary/hypothalamic axis and the ventral optic stalk.

We report on the isolation of a murine homeobox-containing gene, Six6 (Optx2), that shows extended identity in its coding region with Six3, the only member of the mammalian Six gene family known to be expressed in the optic primordium. Phylogenetic analysis demonstrates that Six6 and Six3 belong to a separate group of homeobox-genes that are closely related to the recently identified Drosophila optix. Earliest Six6 expression was detected in the floor of the diencephalic portion of the primitive forebrain, a region predicted to give rise to the neurohypophysis and to the hypothalamus. Later on, Six6 mRNA was found in the primordial tissues giving rise to the mature pituitary: the Rathke's pouch and the infundibular recess. In the optic primordium, Six6 demarcates the presumptive ventral optic stalk and the ventral portion of the future neural retina. In the developing eye. Six6 expression was detected in the neural retina, the optic chiasma and optic stalk, but not in the lens. When compared to Six6, Six3 expression pattern was highly similar, but with a generally broader transcripts distribution in the brain and in the visual system. We finally show that Six6 does not require Pax6 for its expression in the optic primordium, suggesting that Six6 acts on a parallel and/or independent pathway with Pax6 in the genetic cascade governing early development of the eye.

Expanded retina territory by midbrain transformation upon overexpression of Six6 (Optx2) in Xenopus embryos.

During vertebrate eye development, the expression of the homeobox gene Six6 is restricted to the neural retina and is initiated later than Rx and Pax6 in the presumptive retina field. We show here that overexpression of mouse Six6 in Xenopus embryos can induce transformation of competent tissue of the anterior neural plate into retinal tissue. In Six6 injected embryos, the molecular identity of the presumptive midbrain and rostral hindbrain regions was lost, as shown by the absence of XEn-2 and Xpax2 expression, being replaced by the ectopic expression of the retinal markers Xpax6 and Xrx. When allowed to grow further, Six6 injected embryos developed ectopic eye-like structures in the rostral brain and showed a transformation of the midbrain into retina. Similar results were obtained upon overexpression of Six3 or Xsix3, revealing a possible redundance of Six3 and Six6 activities. Taken together, results obtained suggest that during normal retina development, the relatively late expressed Six6 gene becomes part of a network of retinal homeobox genes that are linked together by positive feedback loops. Furthermore, our results demonstrate that the primitive neural ectoderm of the future midbrain and rostral hindbrain is competent to form retinal tissue.

Monoclonal antibodies against isotypic and isoallotypic determinants of human IgA1 and IgA2: fine specificities and binding properties.

We have analysed and compared the fine specificity and behavior in various immunoassays of 10 mouse monoclonal antibodies, from three independent laboratories, directed against IgA1, IgA2 or non-IgA2m(2). The following observations were made. (1) Although all of the monoclonal antibodies were specific for a particular IgA subclass or isoallotype in a radioimmunoassay, three of them were not specific when tested in indirect immunofluorescence on plasma cells derived from pokeweed-activated peripheral blood lymphocytes. In this highly sensitive system, contrary to direct immunofluorescence previously performed using formalin-fixed lymphoid tissue, the anti-IgA1 69.114 reacted with some of the IgA2 plasma cells, the anti-IgA2 DLDB7 reacted with some of the IgA1 plasma cells and the anti-IgA2 16.512 dimly reacted with all IgM plasma cells. (2) Among the eight anti-IgA subclass antibodies, seven were directed against the CH2 domain of IgA whereas the anti-IgA1 1-155-1 recognised an epitope destroyed by Streptococcus sanguis IgA1 protease and localised in the hinge region of IgA1. The two anti-isoallotype antibodies were directed against epitope(s) probably localised in the 65 C-terminal amino acid residues of the alpha-CH3 domain. All of the 10 antibodies were able to react with endogeneously produced surface IgA on B-cells. (3) Using monoclonal anti-IgA subclass antibodies in radioimmunoassay may be hazardous in the absence of knowledge of their affinity constants and of careful control experiments: some of the antibodies were not sensitive in radioimmunoassays designed to measure the serum titer of specific IgA1 and IgA2 antibodies. Moreover, major differences were observed between the different monoclonal reagents with respect to the influence of the size of IgA on a solid-phase sandwich radioimmunoassay. While three of the anti-IgA1 underestimated dimeric IgA relative to monomeric IgA, the fourth anti-IgA1 and all the anti-IgA2 overestimated dimeric IgA relative to monomeric IgA, by a factor sometimes close to 7.

The bone marrow in multiple myeloma: correlation of plasma cell ultrastructure and clinical state.

The bone marrow plasma cells of 52 patients with various kinds of monoclonal gammopathies were studied by electron microscopy, and compared to the bone marrow plasma cells of 22 patients with reactive plasmacytosis. Virtually every marrow from patients with myeloma and macroglobulinemia contained plasma cells with disparity between the nuclear maturation and cytoplasmic differentiation. This asynchronous development was not present in plasma cells of reactive marrows nor in plasma cells from patients with megaloblastic anemias. The degree of asynchrony observed in myeloma and macroglobulinemia was proportional to the extent of disease as judged by clinical criteria. For the most part plasma cells of patients with non-myelomatous monoclonal gammopathy failed to exhibit significant asynchrony. These observations are consistent with the view that multiple myeloma is a neoplastic disorder with a definably malignant-appearing cellular proliferation.

Lipids and stroke: a paradox resolved.

BACKGROUND: Although dyslipidemia is a well established risk factor for coronary artery disease, its relationship to ischemic cerebrovascular disease has remained unclear, perhaps because of the heterogeneous nature of strokes. METHODS: In a case-control study, we measured the serum concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, serum triglycerides, and lipoprotein(a) levels and determined the apolipoprotein E phenotype and serum ferritin level in 90 consecutive systematically investigated patients with stroke or transient ischemic attack of atherothrombotic origin. Ninety age-, sex-, and community-matched subjects served as controls. RESULTS: Plasma total cholesterol (5.99 vs 5.45 mmol/L [232 vs 211 mg/dL], P=.003), low-density lipoprotein cholesterol (3.96 vs 3.45 mmol/L [153 vs 133 mg/dL], P=.004), and serum triglyceride (2.09 vs 1.82 mmol/L [8] vs 70 mg/dL], P=.03) levels were significantly higher among the patients with atherothrombotic strokes and transient ischemic attacks than among the control subjects. The inverse was true for high-density lipoprotein cholesterol (1.07 vs 1.18 mmol/L [41 vs 46 mg/dL], P=.02) levels. No significant differences were found in lipoprotein(a) levels or in the distribution of apolipoprotein E phenotypes or allele frequency. Serum ferritin levels did not differ significantly between patients and control subjects. CONCLUSIONS: Elevated low-density lipoprotein cholesterol and triglyceride levels are significant independent risk factors in patients with proven atherothrombotic cerebrovascular disease manifesting as stroke or transient ischemic attack. The level of stored serum iron, as reflected by serum ferritin levels, does not correlate with the presence of atherothrombotic cerebrovascular or coronary disease.

Leaf carbohydrate status in Lolium temulentum during the induction of flowering.

Unifoliated plants of Lolium temulentum L. ev. Ceres, a qualitative long-day grass, were induced to flower by one 24-h long day (LD) or by one 8-h short day (SD) advanced by 1 2 h in the normal regime, so-called 'displaced short day' (DSD). Standard light for SD and DSD was a mixture of fluorescence and incandescence at 400 µmol m-2 s-1 whereas the extension period of the 24-h LD was solely incandescence at 10-15 µmol m-2 s-1 . The DSD system was first characterized by the timings of floral induction, stimulus translocation and apical development. Carbohydrates in the blade tissues and in leaf exudate were analysed comparatively in vegetative and induced plants. Fructans were not detected in the leaf tissues whereas sucrose and starch were found to be present in similar amounts. In SD, their contents exhibited a diurnal fluctuation and were not in large excess. The common change observed during the two inductive treatments was that starch remained at a high level during the LD extension, even though the lighting was unsuitable for photosynthesis, and increased transiently in DSD. Sucrose was the major sugar contained in the leaf exudate. Its content increased when flowering was induced, but not at the same time in the two systems. In LD, sucrose exudation rose when plants were returned to standard light after the inductive cycle, i.e. after the LD stimulus had left the leaf blade. By contrast, during the DSD, sucrose was transported at the same time as the floral stimulus. Results are discussed together with the methods used to time stimulus translocation and their implications.

On changing curricula: lessons learned at two dissimilar medical schools.

Two dissimilar U.S. medical schools--the University of Pittsburgh School of Medicine and the University of Texas Medical Branch at Galveston-changed their curricula for the first two years of medical education from ones that were lecture-dominated and departmentally run to ones that are centrally governed, multi-modal, goal-oriented, and fully integrated, with mechanisms to continue curricular change into the last two years of medical education. The change at each school was in response to national education philosophy, the recommendations of the Liaison Committee for Medical Education after the most recent site visit, and faculty's and students' concerns and interests. The change process took place over a three- to four-year period at each school, involved students, faculty, and administration, and utilized task forces and retreats as communication vehicles. The barriers encountered (e.g., belief by some that the curriculum needed no change; concern over loss of departments' control) and the processes employed to overcome them and to radically change the curricula (e.g., commitment of the central administration and dean to the change, involvement of all segments of the school in the change process, appointment of department chairs on task forces, and creation of a strong curriculum committee that gave authority to faculty and students) were essentially identical. The resulting curricula were also largely similar in their main characteristics, but there were notable differences, based on the goals and concerns of the two institutions.

The undergraduate medical curriculum: centralized versus departmentalized.

The authors describe the advantages and disadvantages of central governance of the undergraduate medical curriculum as contrasted with traditional departmental approaches, based upon their school's experience with a new centrally governed curriculum during the preceding four years. Central governance has more advantages, but also more costs, compared with traditional departmental approaches. Central governance does what it was intended to do: it provides rational and integrative mechanisms for ensuring a broad general education in medicine focusing on the doctor-patient relationship. It also provides an effective mechanism for dealing with "turf" and time issues in the curriculum while allowing for and encouraging changes and providing mechanisms for evaluating those changes. However, as the allocation of resources and rewards remains more departmentally than centrally based, a major challenge of central governance has been to help faculty resolve a "conflict of loyalty" (the sense of serving two masters) between school and department, particularly in the evaluation and reward of teaching. On balance, central governance provides a powerful means of introducing broad-based reforms into all elements of the undergraduate medical curriculum, but it requires ongoing collaboration with faculty and chairs to assist them in negotiating competing pressures and priorities as they strive to become excellent teachers.

Integrated case studies and medical decision making: a novel, computer-assisted bridge from the basic sciences to the clinics.

This article describes a novel course that was designed to bridge the gap between the basic science years and clinical experiences in medical school by using information science and computer technology as major components of problem-based learning (PBL) sessions. The course, Integrated Case Studies and Medical Decision Making, was first given to second-year students at the University of Pittsburgh School of Medicine in the spring of 1994. It consists of 13 PBL exercises, each of which explores a clinical case. The cases, including images and gated access to information, are housed on a computer. Using one of 16 networked terminals in specially designed small-group rooms, groups of nine students progress through the cases with a faculty facilitator. The responses of students and faculty to the initial year of the course were favorable. In comparison with traditional PBL sessions, enhanced quality of and access to images and accountability for accessing case information in sequential fashion were cited as major strengths of the course. Juxtaposition of basic science and clinical material and utility in reviewing for the United States Medical Licensing Examination were also cited as strengths. The diversity of the basic science material involved in completing the cases drew overwhelming enthusiasm from students and facilitators alike. In conclusion, the course successfully employs computer and information science technology, which will be of increasing importance to future physicians. The course also serves as an effective bridge to the clinical years of medical school and as a study adjunct for the USMLE.

Ecogenetics of Parkinson's disease: prevalence and environmental aspects in rural areas.

We make use of the unique combination of a homogeneous genetic and racial origin in the rural population of Quebec and the facilities of free and universal access to medical care, to study the distribution of the prevalence of Parkinson's disease in the 9 rural hydrographic regions of the Province. Through 3 different methods of ascertainment, confirmed by two control probes, we demonstrate that the prevalence of Parkinson's disease is of uneven distribution within rural areas. We further investigated the characteristics of the regions of high prevalence. These regions which are predominantly agricultural and areas of intensive market gardening were also the areas with the highest use of pesticides.

IgA paraprotein inhibition of human neutrophil chemotaxis. Reduced activity following treatment with IgA-specific protease from Neisseria gonorrhoeae.

Removal of the Fc region of human IgA m components by treatment with IgA-specific protease from Neisseria gonorrhoeae reduces the neutrophil chemotactic inhibitory activity associated with IgA M components. This observation, along with the failure of an IgA halfmer paraprotein to inhibit neutrophil chemotaxis, emphasizes the importance of the IgA Fc region in the inhibition of neutrophil chemotaxis by IgA M components.

Sudden death in turkeys with perirenal hemorrhage: pathological observations and possible pathogenesis of the disease.

A pathological study was conducted on 32 turkeys that died of sudden death with perirenal hemorrhage syndrome. Turkeys were selected from routine necropsy cases in a diagnostic laboratory. A higher incidence was observed in heavy tom turkeys. In addition to the characteristic gross lesions of perirenal hemorrhage, splenomegaly, and pulmonary congestion, turkeys in most cases had a hypertrophic cardiopathy. Microscopic lesions included moderate-to-marked acute passive congestion of all tissues examined (32/32), severe perirenal hemorrhage (32/32), and splenic lymphoid depletion (25/32). Changes in the thyroid follicular epithelium of most birds suggested an increased glandular activity. No lesions suggestive of arterial hypertension were observed. Adenoviral infection was detected in only four of 32 birds. Bacteriological cultures revealed no significant pathogen. Results suggest that sudden death in turkeys with perirenal hemorrhage is caused by an acute congestive heart failure consecutive to a hypertrophic cardiopathy. The perirenal hemorrhage would be a consequence of a severe passive congestion in kidneys.

A generalized inclusion body disease in the budgerigar (Melopsittacus undulatus) caused by a papovavirus-like agent.

High mortality rates have been reported in budgerigars between one and 15 days of age in 19 aviaries in the Province of Quebec. The most consistent signs of disease were abdominal distention, lack of down feathers on the back and abdomen, lack of filoplumes on the head and neck, and retarded growth of the tail and contour feathers in birds that either survived or died later. Internal gross lesions were hydropericardium, enlarged heart and liver with multiple pinpoint white spots or large, yellow foci, pale or congested kidneys, congested lungs, and ascites. Histologic examination revealed large, slightly basophilic inclusion bodies in the enlarged nuclei of many different cells. These inclusion bodies were composed of viral particles. Multiple foci of coagulation necrosis were scattered in the myocardium and liver parenchyma, and granulovacuolar degeneration was common in renal tubular epithelial cells. Ballooning degeneration was multifocal in the epidermis and very extensive in the epithelial cells of developing feather follicles, and this led to their partial or complete destruction. Viral particles 50 to 55 nm in diameter were observed in negatively stained preparations from different organs of affected birds. These particles had the size and morphology of a papovavirus. In experimentally infected 25-day-old budgerigars, histologic examinations revealed the presence of intranuclear inclusions in hepatocytes, epithelial cells of the kidney tubules, and reticular cells of the spleen, despite the absence of clinical signs. We feel that this disease is caused by a papovavirus-like agent that can replicate in many tissues of the body, causing widespread lesions responsible for the high mortality rate of very young budgerigars and for the absence and/or incomplete development of feathers.

Papovavirus induced feather abnormalities and skin lesions in the budgerigar: clinical and pathological findings.

Feather abnormalities and skin lesions caused by a papovavirus infection in budgerigars are described. Diseased one to 15 day old birds displayed a lack of nestling down feathers and filoplumes on the head and neck. Survivors older than 15 days exhibited retarded growth and temporary absence of feathers variable from bird to bird. Several birds between 15 and 25 days of age had flight feathers with total absence or marked sparseness of the vanes. After 25 days, feathers began to grow, although the tail and/or some flight feathers of some of the birds remained underdeveloped or absent for several weeks. Several of these affected birds were unable to fly and are called "runners"Microscopic lesions in the feather follicles of the affected birds less than 15 days of age, were characterized by focal, multifocal or diffuse ballooning degeneration in the lateral and axial plate cells of the barb ridges with the presence of large basophilic or amphophilic intranuclear inclusions in the same cells. Focal areas of ballooning degeneration with intranuclear inclusions were also found in the epidermis. Clinical observations made on these birds are compared with those reported in the literature for French molt.